The cell surface glycoprotein CD4 is the cellular receptor for the human immunodeficiency virus (HIV) and binds with high affinity to the HIV envelope glycoprotein, gp 120. Inhibition of the binding of HIV gp120 to CD4 on the Surface of target CeLls, as well as inhibition of gpl20-CD4-mediated cell fusion between uninfected and uninfected cells, are very promising approaches to the treatment of HIV infection. The purpose of this Phase I SBIR proposal is to develop a screening assay to detect inhibitors of the interaction of HIV gpl2O with CD4. The development of the assays described in this proposal will enable tile large-scale automated screening and identification in Phase 11 of potential anti-HIV therapeutics. These inhibitors will be important candidates for further in vitro analysis as well as in vivo and clinical evaluation.